1. Field of the Invention
The present invention is broadly concerned with improved, stable, complexing agent-iodine germicidal compositions and concentrates that can be diluted to provide such compositions, useful for topical applications to the skin of human or animals, having relatively low complexing agent(s)/average available iodine ratios. More particularly, it is concerned with such concentrates and use compositions wherein the complexing agent(s)/average available iodine ratio ranges from about 2:1 to about 4.5:1, and wherein the complexing agent fraction preferably comprises a polyoxypropylene-polyoxyethylene block copolymer having a central polyoxypropylene (POP) molecular weight of at least about 2600 and a polyoxyethylene (POE) content on the order of 30%-75% by weight. Use of specific complexing agents of this character has been found to yield low ratio, high and low temperature stable germicidal use compositions and concentrates. In another aspect of the invention, use compositions and concentrates are provided with from about 2-4.5 parts of a two-component complexing agent per part of available iodine, and wherein the complexing agent includes individual amounts of polyvinyl pyrrolidone (i.e. Povidone or PVP), and a compatible, nonionic, surfactant complexor, such as a polyethoxylated polyoxypropylene.
2. Description of the Prior Art
Germicidal detergent-iodine products designed for topical application to the skin have long been available. These formulations are used primarily in products such as pre-operative antiseptic preparations, hand cleaners and in bovine teat dips for mastitis prevention. Apart from complexed detergent-iodine, these products typically include variable amounts of additives to provide pH control, emolliency, viscosity, and in some cases a colorant.
It has also been known to provide Povidone-iodine germicidal compositions for topical uses. Generally, these prior compositions are characterized by relatively high levels of Povidone (e.g., a minimum of about 6:1 Povidone:iodine ratio), which have been thought necessary in order to adequately complex the iodine, particularly for human topical use products.
U.S. Pat. No. 3,728,449 describes a wide range of detergent-iodine germicidal compositions specifically adapted for application to the teats of milk animals for the control and prevention of mastitis. A number of ethoxylated nonionic iodine complexing agents are disclosed as being effective in the '449 patent, at a minimum ratio of 5 parts complexing agent to each part of average available iodine. Among the complexing agents described in this patent are the nonylphenol ethoxylates, polyalkylene glycol ethers, polyoxyethylene sorbitan monolaurate and monopalmitate, polyvinylpyrrolidone and polyethoxylated polyoxypropylenes. This latter type of complexing agent is referred to in the art as a "Poloxamer", which is a block copolymer based on a central polyoxypropylene moiety with polyoxyethylene groups at the respective ends of the central moiety. There are a wide range of commercially available Poloxamers having central moieties ranging in molecular weight from about 1000 to 4000, and containing polyoxyethylene contents on the order of 10%-80% by weight of the total weight of the Poloxamer.
In order to be dependable and useful to an end user, detergent-iodine germicidal use compositions and concentrates must be stable (i.e., remain homogeneous) over a wide range of temperature. If stability is lost, and the products separate, the utility of the compositions is significantly degraded and they can present a potential hazard to the user. Generally speaking, stability in this context means that a given product must remain homogeneous after extended storage (e.g., 1 week) at temperatures as low as 2.degree. C. (which may be experienced in cold warehouse storage areas) or as high as 40.degree. C., which can occur during transport in closed vehicles. Furthermore, although a given product may separate when frozen, especially after undergoing several freeze-thaw cycles, it should be readily reconstitutable as a homogeneous mixture upon simple shaking or mixing.
In addition, all detergent-iodine formulations have some iodide ion present, which can vary as desired from relatively high concentrations described in U.S. Pat. No. 3,028,299 to relatively low, stabilized values taught in U.S. Pat. No. 4,271,149. In general, iodide ion levels range from about 0.3-1 part iodide per part of iodine in prior formulations.
As indicated above, detergent-iodine products designed for topical application to the skin are normally formulated with an amount of emollient. The most common emollients employed are glycerin, lanolin and its derivatives, sorbitol, fatty acid esters of polyhydroxylated compounds, and propylene glycol. These emollients are used at levels ranging from below 1% to as much as 10% in use compositions. Glycerin is the most widely used emollient in bovine teat dips and is also used extensively at low levels in human topical povidone-iodine and deter- gent-iodine formulations.
Another desirable functional characteristic for detergent-iodine germicidal compositions designed for topical application, is the ability to spread evenly on the skin and not drain off so rapidly as to prevent insufficient germicidal contact time. Many of the usual ingredients in detergent-iodine products contribute to viscosity. However, it is common for topical products to be formulated with a specific thickener to provide added viscosity. There are many viscosity modifiers compatible with detergent-iodine systems, such as carboxymethylcellulose derivatives, polyacrylate derivatives, alginates, xanthates and polysaccharides. These are typically used at levels below 1% by weight in a final use composition. These types of ingredients, properly selected, have an insignificant effect on the homogeneity of a given use composition. On the other hand, where dilutable concentrates are desired, viscosity-modifying additives can become a problem and special care must be taken in the selection of specific agents and their levels of use in concentrates.
As explained above, the prior art is replete with examples of detergent-iodine formulations having relatively high detergent/average available iodine ratios in excess of 5:1. Patent No. 3,728,449 describes a single example at a ratio of 5:1, which makes use of PVP as a complexing agent. The next lowest ratio example in this patent uses a nonylphenol ethoxylate at a ratio of 7.5:1. Example IIID describes a composition made up to include 5 parts of a Poloxamer (Pluronic P123), but the total detergent/average available iodine ratio of this example is 8:1.
There are a number of potential advantages in the use of very low complexor/average available iodine ratios in germicidal iodine concentrates and use compositions designed for skin or tissue application. For example, in a low ratio product of this type, there would be less organic matter to react with the iodine, thereby rendering such compositions more stable relative to the labeled or nominal available iodine content. Another advantage where the principal complexor is a detergent is that reduced amounts of detergent would be expected to be less irritating to the skin and would accordingly require a lesser amount of emollient. Compositions with lower complexor/average available iodine ratios could be formulated to have higher, and more stable, free or uncomplexed iodine levels. The use of minimal amounts of complexor also would allow for the possibility of reduced water content in concentrates, thereby correspondingly reducing packaging, shipment and storage costs.
Iodine-containing compositions have also been provided in the past which include polyvinyl pyrrolidone. Such compositions, especially those conforming to U.S.P. requirements for Povidone-iodine topical solutions, have high ratios of Povidone to available iodine within the range of from about 9:1 to about 7:1. Most commercial compositions of this character also contain a small amount of surface active agent, generally about 1% or less, to lower the surface tension and thereby aid in spreading. Such a surfactant additive is frequently of the ethoxylated nonionic type, most frequently based upon a nonylphenol ethoxylate. With ratios of Povidone to iodine in the aforementioned range, the iodine complexing contribution of the small amount of nonionic surfactant employed is minimal at best.
A Poloxamer-iodine topical antiseptic ("Prepodyne") has been available for years for use in hospitals.
This composition has a Poloxamer to available iodine ratio of about 5:1, utilizing Poloxamers with an average polyoxypropylene molecular weight of around 2600. However, there are no known prior compositions containing a two-component iodine complexor comprising Povidone and a nonionic surfactant, where the total iodine complexor:iodine ratio is less than 5:1.
Accordingly, there is a real and unsatisfied need in the art for improved, low ratio complexor-iodine use compositions (and their dilutable concentrate counter-parts) which have the requisite stability and germicidal utility and which can be applied directly to animal or human skin.